2-177265309-T-G

Position:

• chr2-177265309-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000428541.1(ENSG00000222043):​n.364-71T>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 213,946 control chromosomes in the GnomAD database, including 82,704 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.88 (59765 hom., cov: 34)
  • Exomes 𝑓: 0.86 (22939 hom.)
• Consequence: ENST00000428541.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

Genes affected

(HGNC:):

NFE2L2 (HGNC:7782): (NFE2 like bZIP transcription factor 2) This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. The encoded transcription factor regulates genes which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to injury and inflammation which includes the production of free radicals. Multiple transcript variants encoding different isoforms have been characterized for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000428541.1	n.364-71T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134590 AN: 152168 Hom.: 59705 Cov.: 34

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.848

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.891

GnomAD4 exome AF: 0.861 AC: 53083 AN: 61660 Hom.: 22939 Cov.: 0 AF XY: 0.862 AC XY: 24836 AN XY: 28822

Gnomad4 AFR exome AF: 0.932

Gnomad4 AMR exome AF: 0.854

Gnomad4 ASJ exome AF: 0.879

Gnomad4 EAS exome AF: 0.728

Gnomad4 SAS exome AF: 0.862

Gnomad4 FIN exome AF: 0.862

Gnomad4 NFE exome AF: 0.884

Gnomad4 OTH exome AF: 0.886

GnomAD4 genome AF: 0.885 AC: 134704 AN: 152286 Hom.: 59765 Cov.: 34 AF XY: 0.881 AC XY: 65607 AN XY: 74458

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.877

Gnomad4 EAS AF: 0.730

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.848

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.893

Alfa AF: 0.885 Hom.: 11831

Bravo AF: 0.886

Asia WGS AF: 0.820 AC: 2853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6721961; hg19: chr2-178130037;